text: Deficiency of expression of a DNA repair gene occurs in many cancers (see DNA repair defect and cancer risk and microRNA and DNA repair).  Altered microRNA (miRNA) expression that either decreases accurate DNA repair or increases inaccurate microhomology-mediated end joining (MMEJ) DNA repair is often observed in cancers.  Deficiency of accurate DNA repair may be a major source of the high frequency of mutations in cancer (see mutation frequencies in cancers).  Repression of DNA repair genes in cancers by changes in the levels of microRNAs may be a more frequent cause of repression than mutation or epigenetic methylation of DNA repair genes.
  For instance, BRCA1 is employed in the accurate homologous recombinational repair (HR) pathway.  Deficiency of BRCA1 can cause breast cancer.  Down-regulation of BRCA1 due to mutation occurs in about 3% of breast cancers.  Down-regulation of BRCA1 due to methylation of its promoter occurs in about 14% of breast cancers.  However, increased expression of miR-182 down-regulates BRCA1 mRNA and protein expression, and increased miR-182 is found in 80% of breast cancers.
  In another example, a mutated constitutively (persistently) expressed version of the oncogene c-Myc is found in many cancers. Among many functions, c-Myc negatively regulates microRNAs miR-150 and miR-22.  These microRNAs normally repress expression of two genes essential for MMEJ, Lig3 and Parp1, thereby inhibiting this inaccurate, mutagenic DNA repair pathway.  Muvarak et al. showed, in leukemias, that constitutive expression of c-Myc, leading to down-regulation of miR-150 and miR-22, allowed increased expression of Lig3 and Parp1.  This generates genomic instability through increased inaccurate MMEJ DNA repair, and likely contributes to progression to leukemia.
  To show the frequent ability of microRNAs to alter DNA repair expression, Hatano et al.  performed a large screening study, in which 810 microRNAs were transfected into cells that were then subjected to ionizing radiation (IR).  For 324 of these microRNAs, DNA repair was reduced (cells were killed more efficiently by IR) after transfection.  For a further 75 microRNAs, DNA repair was increased, with less cell death after IR.  This indicates that alterations in microRNAs may often down-regulate DNA repair, a likely important early step in progression to cancer.